ABSTRACT At least 5 million workers in the United States from several sectors are potentially exposed to airborne endotoxin. Acute endotoxin exposure produces features of dynamic airflow obstruction. However, the health effects of long-term exposure remain unclear. A few studies of chronic endotoxin exposure have identified an accelerated decline in forced expiratory volume at 1 second (FEV1), a hallmark of chronic obstructive pulmonary disease (COPD). Even studies of chronic exposure, though, tend to span less than a decade, and little is known about the trajectory of lung disease after exposure cessation, the mechanisms underlying disease severity, and the extra-pulmonary effects of chronic exposure. The goal of this competing continuation is to complete a 36-year longitudinal study of a stable, closed cohort of 919 textile workers living in the same geographical region of Shanghai, China. This unique cohort comprises cotton workers exposed to high levels of workplace endotoxin with matched control silk workers exposed to non-detectable levels of endotoxin, both with a high proportion of lifetime non-smokers. Since 1981, they have been evaluated for dust and endotoxin exposure and respiratory outcomes. All workers are now retired, but 74.2% of those still alive participated in the 30-year survey, with comparable follow-up participation expected at 35 years. The previous continuation cycle of this study enabled us to describe the persistent deleterious effects of workplace endotoxin even after worker retirement. Adverse respiratory effects include impaired lung function recovery with accelerated FEV1 decline, increased airway narrowing, and increased lung mass and lung density on chest computed tomography (CT), which likely represents persistent lung inflammation. These findings raise new questions: whether persistent inflammation plays a role in disease progression, whether disease is reversible after exposure cessation, and whether long-term endotoxin exposure leads to extra-pulmonary disease. Our overarching hypothesis is that prior cumulative workplace endotoxin exposure leads to persistent lung disease after exposure cessation due to systemic, lung parenchymal, and airway inflammation, and also results in extra-pulmonary health effects. This revised proposal has expanded its scope in response to critiques to evaluate a dense panel of inflammatory biomarkers, as well as consideration of air pollution and other variables important to study generalizability. Our research results are essential to devising effective preventive programs. The NORA sectors addressed in this proposal include: agriculture, manufacturing, healthcare, services, and construction. The cross-sector programs addressed are respiratory disease and global collaborations.